Toddalolactone protects against osteoarthritis by ameliorating chondrocyte inflammation and suppressing osteoclastogenesis.
Toddalolactone protects against osteoarthritis by ameliorating chondrocyte inflammation and suppressing osteoclastogenesis.
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Toddalolactone 通过改善软骨细胞炎症和抑制破骨细胞生成来预防骨关节炎
DOI：
10.1186/s13020-022-00576-w
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发表时间：
2022-02-05
期刊：
影响因子：
4.9
通讯作者：
Sang W
中科院分区：
文献类型：
--
作者：
Xu Y;Xue S;Zhang T;Jin X;Wang C;Lu H;Zhong Y;Chen H;Zhu L;Ma J;Sang W
骨关节炎（OA）是最常见的慢性关节疾病，伴有进行性软骨和软骨下骨损伤。飞龙掌血内酯（Toddalolactone，TOD）是从飞龙掌血（Toddalia asiatica（L.）拉姆，已广泛用于治疗中风、类风湿性关节炎和水肿。然而，TOD在OA发病和进展中的作用尚未见报道。在这项研究中，我们的目的是确定如何在体外和体内影响骨关节炎。使用LPS（10 µg/ml）和IL-1β（10 ng/ml）诱导软骨细胞炎症或RANKL诱导骨髓源性巨噬细胞（BMSCs）中的破骨细胞分化。评价了TOD对软骨细胞炎症和破骨细胞分化的影响。采用前交叉韧带切断术（ACLT）建立OA动物模型并研究TOD的影响。我们发现，在体外，TOD抑制炎症和分解代谢介质（IL-6，IL-8，TNF-α，MMP 2，MMP 9和MMP 13）在炎症软骨细胞中的表达。此外，已证明TOD抑制RANKL诱导的破骨细胞生成并抑制破骨细胞标志物基因的表达。我们的数据还证实了TOD通过抑制NF-κB和MAPK信号通路的激活来抑制关节软骨的破坏和破骨细胞的生成。在ACLT小鼠模型中，我们发现TOD减弱软骨侵蚀并抑制骨吸收。这些结果表明，TOD可以作为一种潜在的治疗OA的药物。在线版本包含补充材料，可通过10.1186/s13020-022-00576-w获得。
Osteoarthritis (OA) is widely recognized as the most common chronic joint disease accompanied by progressive cartilage and subchondral bone damage. Toddalolactone (TOD), a natural compound extracted from Toddalia asiatica (L.) Lam., has been widely used in the treatment of stroke, rheumatoid arthritis, and oedema. Nevertheless, what TOD acts as in the pathogenesis and progression of OA hasn’t been reported. In this investigation, we have aimed to determine how TOD affects OA in vitro and in vivo. LPS (10 µg/ml) and IL-1β (10 ng/ml) were employed to induce chondrocyte inflammation or RANKL to induce osteoclast differentiation in bone marrow derived macrophages (BMMs). The effects of TOD on chondrocyte inflammation and osteoclast differentiation were evaluated. Anterior cruciate ligament transection (ACLT) was performed to develop an OA animal model and study the effects of TOD. We found that TOD inhibited the expression of inflammatory and catabolic mediators (IL-6, IL-8, TNF-α, MMP2, MMP9, and MMP13) in inflammatory chondrocytes in vitro. Furthermore, TOD was proven to inhibit RANKL-induced-osteoclastogenesis and inhibit the expression of osteoclast marker genes. Our data also confirmed that TOD suppressed the destruction of articular cartilage and osteoclastogenesis via inhibiting the activation of NF-κB and MAPK signalling pathways. In the ACLT mouse model, we found that TOD attenuated cartilage erosion and inhibited bone resorption. These results showed that TOD can be adopted as a potential therapeutic agent for OA. The online version contains supplementary material available at 10.1186/s13020-022-00576-w.